新型哒嗪并[4,5-b]吲哚-4-酮和哒嗪-3(2H)-酮类似物作为DYRK1A抑制剂的合成
Synthesis of new pyridazino[4,5-b]indol-4-ones and pyridazin-3(2H)-one analogs as DYRK1A inhibitors.
作者信息
Bruel Amélie, Bénéteau Romain, Chabanne Mylène, Lozach Olivier, Le Guevel Rémy, Ravache Myriam, Bénédetti Hélène, Meijer Laurent, Logé Cédric, Robert Jean-Michel
机构信息
Université de Nantes, Nantes Atlantique Universités, Laboratoire de Chimie Thérapeutique, Cibles et Médicaments des Infections et du Cancer, IICIMED-EA 1155, UFR Sciences Pharmaceutiques, 1 rue Gaston Veil, Nantes F-44035 Cedex 1, France.
Protein Phosphorylation & Human Disease Group, CNRS, USR 3151, Station Biologique, B.P. 74, 29682 Roscoff Cedex, France.
出版信息
Bioorg Med Chem Lett. 2014 Nov 1;24(21):5037-40. doi: 10.1016/j.bmcl.2014.09.017. Epub 2014 Sep 16.
New pyridazino[4,5-b]indol-4-ones and pyridazin-3(2H)-one analogs were synthesized and their inhibitory activities against DYRK1A, CDK5/p25, GSK3α/β and p110-α isoform of PI3K evaluated using harmine as reference. Both furan-2-yl 10 and pyridin-4-yl 19 from the two different series, exhibited submicromolar IC50 against DYRK1A with no activities against the three other kinases. In addition, compound 10 exhibited antiproliferative activities in the Huh-7, Caco2 and MDA-MB-231 cell lines.
合成了新型哒嗪并[4,5 - b]吲哚 - 4 - 酮和哒嗪 - 3(2H)-酮类似物，并以 harmine 作为对照评估了它们对 DYRK1A、CDK5/p25、GSK3α/β 和 PI3K 的 p110 - α 亚型的抑制活性。来自两个不同系列的呋喃 - 2 - 基 10 和吡啶 - 4 - 基 19 对 DYRK1A 表现出亚微摩尔级的 IC50，对其他三种激酶无活性。此外，化合物 10 在 Huh - 7、Caco2 和 MDA - MB - 231 细胞系中表现出抗增殖活性。
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